The proposed work addresses a key goal of NIMH Program Announcement PA-07-312, which seeks to enhance scientific understanding about the etiology of psychopathology related to violence and trauma". The almost 4000 missiles that fell within Northern Israel in the summer of 2006, the damage suffered by property and persons, and the confinement of many families in bomb shelters during the terror period created a unique 'naturalistic'laboratory for assessing the effects of PTSD caused by exposure to a circumscribed period of terror. Within this context, we will examine the health and behavior of fetuses and birth parameters of pregnant women who were residents of the North at the time of the war and test for gene and environmental moderation of fetal and birth measures. We will study two groups: (1) 150 women who are residents of cities attacked during the "war" and who meet full criteria for posttraumatic stress disorder (PTSD) as a result of their exposure to attacks, and (2) 150 women from the same cohort, who show no symptoms of PTSD. The study will be the first study to examine fetal health and behavior in pregnant women with PTSD and the first study to test for gene-based vulnerabilities and Gene x Environment on these measures. The study speaks to the impact of terror induced PTSD on fetal development, the potential transmission of biological events associated with PTSD from mother to fetus, and environmental and genetic factors that may exacerbate fetal risk. The specific aims of the study are: Aim 1. Fetal health and behavior will be adversely affected by maternal PTSD. Hypothesis 1 asserts that fetuses of mothers exposed to terror and suffer from PTSD will show signs of poorer health (stunted fetal growth measures, atypical reactivity and regulation of heart rate and torso/limb movement to challenge, and complications) and poorer birth/neonatal parameters (birth weight, head circumference, gestational age at delivery, and complications) than women who were exposed to terror, but who do not develop PTSD. We also predict an association between posttraumatic stress symptoms and outcome measures, across the sample. Aim 2. Psychosocial stresses and maternal depression predict fetal health, behavior, and stress reactivity and regulation. Hypothesis 2 posits that, among women with PTSD, psychosocial stressors (life events, chronic stressors) and maternal depression will add significant risk to their fetus. Hypothesis 3 predicts that, in the full sample, psychosocial stress and maternal depression will moderate the effects of maternal PTSD. Aim 3. Analyses of candidate gene associations with fetal/neonatal outcomes. We will evaluate the association between offspring's genotype (indexed by a battery of candidate genes) and fetal/neonatal outcomes. Hypothesis 4 predicts that variants of these genes will have main effects on infant outcomes. Hypothesis 5 predicts we will find gene-environment interactions as follows: a) risk variants implicated in hypothesis 4 will moderate the impact that mothers'PTSD and mother's psychosocial stress each have on fetal/neonatal outcomes (i.e., we expect to observe gene-environment interactions). PUBLIC HEALTH RELEVANCE PARAGRAPH: The violence outside the home, as experienced in some US communities (sporadic and frequent) can affect anyone near by. Information regarding the relation between exposure to violence and PTSD on fetal development and birth outcome is important for understanding the processes that can promote developmental risk in communities with such violence. In this regard, the distribution of adverse reproductive health outcomes in the US and other developed nations is characterized by large racial/ethic disparities (Anachebe 2003). In the US, an almost two-fold disparity persists in the rate of premature birth between African American and non-Hispanic White women, even after accounting for obstetric, socio demographic, and behavioral risk factors (Collins &Hammond 1996;MacDorman et al 2002);and it has been suggested that differences in risk may be related to variations in stress and stress physiology (Wadwa et al 2001). The results of the proposed study, which examines genetic and environmental risk in relation to fetal health, can further understanding of individual differences in psycho- neuroendocrine processes that underlie or contribute to the risk of pre maturity and adverse neurodevelopment, and both represent major public health issues in the US.